Neural Regeneration Research ›› 2017, Vol. 12 ›› Issue (12): 2092-2099.doi: 10.4103/1673-5374.221169

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Notch pathway inhibitor DAPT enhances Atoh1 activity to generate new hair cells in situ in rat cochleae

Wen-wei Luo1, 2, Zhao Han1, 2, Dong-dong Ren1, 2, Xin-wei Wang1, 2, Fang-lu Chi1, 2, Juan-mei Yang1, 2   

  1. 1 Department of Otolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, China
    2 Research Institute of Otolaryngology, Fudan University, Shanghai, China
  • Received:2017-10-25 Online:2017-12-15 Published:2017-12-15
  • Contact: Fang-lu Chi or Juan-mei Yang,Ph.D., chifanglu@126.com or yangjuanmei1982@126.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81420108010, 81271084, 81200740, 81371093.

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Abstract:

Atoh1 overexpression in cochlear epithelium induces new hair cell formation. Use of adenovirus-mediated Atoh1 overexpression has mainly focused on the rat lesser epithelial ridge and induces ectopic hair cell regeneration. The sensory region of rat cochlea is difficult to transfect, thus new hair cells are rarely produced in situ in rat cochlear explants. After culturing rat cochleae in medium containing 10% fetal bovine serum, adenovirus successfully infected the sensory region as the width of the supporting cell area was significantly increased.Adenovirus encoding Atoh1 infected the sensory region and induced hair cell formation in situ. Combined application of the Notch inhibitor DAPT and Atoh1 increased the Atoh1 expression level and decreased hes1 and hes5 levels, further promoting hair cell generation. Our results demonstrate that DAPT enhances Atoh1 activity to promote hair cell regeneration in rat cochlear sensory epithelium in vitro.

Key words: nerve regeneration, Atoh1, DAPT, transdifferentiation, gamma secretase inhibitor, cochlea, sensory epithelium, fetal bovine serum, hair cell, supporting cell, hair cell regeneration, neural regeneration